Acid-Buffering Gel Microbicide Used With Diaphragm May Be a Safe Contraceptive  CME

News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD
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September 11, 2007 — An acid-buffering gel microbicide used with a diaphragm is a safe, acceptable contraceptive with efficacy comparable to that of a common commercial spermicide with diaphragm, according to the results of a multicenter, randomized, double-masked trial published in the September issue of Obstetrics & Gynecology.

"Women need products that protect against both pregnancy and sexually transmitted infections, including human immunodeficiency virus (HIV)," write Kurt T. Barnhart, MD, MSCE, from the University of Pennsylvania in Philadelphia, and colleagues. "The acid buffering gel is a nondetergent spermicide that may provide this dual protection by reinforcing normal vaginal acidity to inactivate both sperm and acid-sensitive sexually transmitted pathogens. The objective of this study was to assess the gel's contraceptive effects, safety, and acceptability."

In this noninferiority study at 11 centers, 621 women who used an acid-buffering gel plus diaphragm were compared with 300 women who used a nonoxynol-9 spermicide plus diaphragm. The initial trial lasted 6 months, and a double-masked extension followed up 234 women for an additional 6 months of use.

For acid-buffering gel, the 6-month pregnancy rate per 100 women was 10.1% (95% confidence interval [CI], 7.1% - 13.1%) compared with 12.3% (95% CI, 7.7% - 16.9%) for nonoxynol-9 spermicide users (difference, –2.2%; 95% CI, –7.7% to 3.3%). For women who used the contraceptive consistently and correctly, based on diary entries, 6-month pregnancy rates were 4.7% for acid-buffering gel and 6.1% for nonoxynol-9 spermicide. Both groups had similar adverse events and acceptability. During the 12-month study, rates of pregnancy were similar in both groups.

"An acid buffering gel used with a diaphragm is a safe, acceptable contraceptive with efficacy comparable to that of a common commercial spermicide with diaphragm," the authors write.

Study limitations include reliance on patient diaries for determination of correct and consistent use, relatively small number of cycles studied for women who consistently and correctly used either product for more than 6 months, and 12% loss to follow-up.

"Sperm and many sexually transmitted pathogens are acid-sensitive, and the acid buffering gel has been reported to be effective in animal models for contraception, herpes simplex virus, chlamydia, gonorrhea, papillomavirus, and HIV-infected leukocytes," the authors conclude. "Additional clinical studies will assess whether it can provide disease protection in women. These data represent a paramount first step in the development of female-controlled product providing dual protection from pregnancy and sexually transmitted infection."

The Contraceptive Clinical Trials Network from the National Institutes of Health supported this study. ReProtect, Inc, provided BufferGel, the acid-buffering gel microbicide. Johnson & Johnson provided Gynol II and OrthoFlex diaphragms. Some of the authors have disclosed various financial relationships, including employment in one case, with Personal Care Products, Johnson & Johnson, and/or ReProtect, Inc.

Obstet Gynecol. 2007;110:577-586.

Clinical Context

Advantages of female barrier contraceptives, such as spermicides, female condoms, diaphragms, and cervical caps, include over-the-counter availability, local action, rapid reversibility, and female control of the method. Vaginal methods may also provide women dual protection against pregnancy and sexually transmitted infections. Although currently available, detergent-based spermicides disrupt the cell membranes of sperm as well as those of HIV and other sexually transmitted pathogens, they can also disrupt cervical and vaginal epithelial cells, harming protective cell layers and causing inflammation.

Nonoxynol-9 is no longer advocated as a microbicide candidate and is thought by some to be inappropriate even as a contraceptive for women at high risk for HIV or other sexually transmitted infections. There is therefore a need for safer spermicides, especially those that could be used as vaginal microbicides. This study compared the efficacy and safety of an acid-buffering gel, nondetergent spermicide, plus diaphragm with that of nonoxynol-9 spermicide plus diaphragm.

Study Highlights

• Between October 2001 and August 2004, women at 11 US centers were randomized in a 2:1 ratio to use of an acid-buffering gel microbicide plus diaphragm (target enrollment, 650; evaluable, n = 621) or nonoxynol-9 spermicide plus diaphragm (target enrollment, 325; evaluable, n = 300).
• Inclusion criteria were being a sexually active female, aged 18 to 40 years, at risk for pregnancy and desiring contraception; having normal (24- to 35-day) menstrual cycles; being willing to engage in at least 4 acts of sexual intercourse per month; using the test products as the primary method of contraception; accepting a moderate risk for pregnancy; and committing to keep a diary of coital activity, product use, and adverse events. Other criteria were being at low risk for HIV or other sexually transmitted infection.
• Exclusion criteria were allergy or sensitivity to spermicides or latex, history of toxic shock syndrome, 2 or more urinary tract infections in the past year, history of infertility, any contraindication to pregnancy, abnormal cervical cytology within the past 12 months, or a sexually transmitted infection diagnosed within the previous 6 months.
• Participants were mostly young, white, unmarried nonsmokers who lived with their partners.
• The initial double-masked, noninferiority study trial lasted 6 months, and a double-masked extension followed up 234 women for an additional 6 months of use. The main endpoint was contraceptive efficacy; secondary endpoints included safety; incidence of vaginal or cervical lesions and irritation; incidence of urinary tract infections, bacterial vaginosis, symptomatic yeast vaginitis, asymptomatic vaginal yeast colonization, and vaginal Escherichia coli colonization; and product acceptability.
• For acid-buffering gel, the 6-month pregnancy rate per 100 women was 10.1% (95% CI, 7.1% - 13.1%) compared with 12.3% (95% CI, 7.7% - 16.9%) for nonoxynol-9 spermicide users (difference, –2.2%; 95% CI, –7.7% to 3.3%).
• For women who used the contraceptive consistently and correctly, based on diary entries, 6-month pregnancy rates were 4.7% for acid-buffering gel and 6.1% for nonoxynol-9 spermicide users.
• During the 12-month study, rates of pregnancy were similar in both groups.
• Estimates of differences between the 2 products were similar in the intent-to-treat population, modified intent-to-treat population, and consistent-and-correct-use analyses.
• Both groups had similar adverse events. Common events included vaginal symptoms, as well as general complaints such as upper respiratory tract infection not thought to be related to product use.
• During use of either product, there was no increase from baseline in the number of women with lesions found on colposcopy. Incidence rates of bacterial vaginosis and vulvovaginal fungal infection were low and similar in each group.
• Changes in vaginal microflora were minimally different between products or from baseline values. In the acid-buffering gel group, there were fewer symptomatic urinary tract infections and less frequent recovery of Ureaplasma urealyticum vs in the nonoxynol-9 spermicide group.
• Acceptability was also similar in both groups, with about two thirds of women in both groups reporting strongly or somewhat liking the method and 17% and 14% in acid-buffering gel and nonoxynol-9 spermicide groups, respectively, reporting somewhat or strongly disliking the method.

Pearls for Practice

• For women who used the contraceptive consistently and correctly, pregnancy rates were 4.7% for acid-buffering gel plus diaphragm and 6.1% for nonoxynol-9 spermicide plus diaphragm.
• Both groups had similar adverse events and acceptability. Common events included vaginal symptoms.

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